Search results for "Blastoma"
showing 10 items of 603 documents
Reducing the effect of beauvericin on neuroblastoma SH-SY5Y cell line by natural products
2020
Abstract In the present work, different natural compounds from coffee by-product extracts (coffee silverskin and spent coffee) rich in polyphenols, was investigated against beauvericin (BEA) induced-cytotoxicity on SH-SY5Y cells. Spent coffee arise as waste products through the production of instant coffee and coffee brewing; while the silverskin is a tegument which is removed and eliminated with toasting coffee grains. First of all, polyphenol extraction methods, measurement of total polyphenols content and its identification were carried out. Afterwards evaluating in vitro effects with MTT assay on SH-SY5Y cells of coffee by-product extracts and mycotoxins at different concentrations and …
Tocotrienol Affects Oxidative Stress, Cholesterol Homeostasis and the Amyloidogenic Pathway in Neuroblastoma Cells: Consequences for Alzheimer’s Dise…
2016
One of the characteristics of Alzheimer´s disease (AD) is an increased amyloid load and an enhanced level of reactive oxidative species (ROS). Vitamin E has known beneficial neuroprotective effects, and previously, some studies suggested that vitamin E is associated with a reduced risk of AD due to its antioxidative properties. However, epidemiological studies and nutritional approaches of vitamin E treatment are controversial. Here, we investigate the effect of α-tocotrienol, which belongs to the group of vitamin E, on AD-relevant processes in neuronal cell lines. In line with the literature, α-tocotrienol reduced the ROS level in SH-SY5Y cells. In the presence of tocotrienols, cholesterol…
Chemoprevention and therapeutic role of essential oils and phenolic compounds: Modeling tumor microenvironment in glioblastoma
2021
Glioblastoma (GBM) is the most common primary tumor of the central nervous system. Current treatments available for GBM entails surgical resection followed by temozolomide chemotherapy and/or radiotherapy, which are associated with multidrug resistance and severe side effects. While this treatment could yield good results, in almost all cases, patients suffer from relapse, which leads to reduced survival rates. Thus, therapeutic approaches with improved efficiency and reduced off-target risks are needed to overcome these problems. Regarding this, natural products appear as a safe and attractive strategy as chemotherapeutic agents or adjuvants in the treatment of GBM. Besides the increasing …
Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology.
2018
Abstract Introduction Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. Adaptogens stimulate cellular and organismal defense systems by activating intracellular and extracellular signaling pathways and expression of stress-activated proteins and neuropeptides. The effects adaptogens on mediators of adaptive stress response and longevity signaling pathways have been reported, but their stress-protective mechanisms are still not fully understood. Aim of the study The aim of this study was to identify key molecular mechanisms of adaptogenic plants traditionally used to treat stress and aging-related disorders, i.e., Rhodiola r…
The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.
2016
KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. M…
Intratumoral Heterogeneity and Longitudinal Changes in Gene Expression Predict Differential Drug Sensitivity in Newly Diagnosed and Recurrent Gliobla…
2020
Background: Inevitable recurrence after radiochemotherapy is the major problem in the treatment of glioblastoma, the most prevalent type of adult brain malignancy. Glioblastomas are notorious for a high degree of intratumor heterogeneity manifest through a diversity of cell types and molecular patterns. The current paradigm of understanding glioblastoma recurrence is that cytotoxic therapy fails to target effectively glioma stem cells. Recent advances indicate that therapy-driven molecular evolution is a fundamental trait associated with glioblastoma recurrence. There is a growing body of evidence indicating that intratumor heterogeneity, longitudinal changes in molecular biomarkers and spe…
Stage 4S neuroblastoma tumors show a characteristic DNA methylation portrait
2016
Stage 4S neuroblastoma (NB) is a special type of NB found in infants with metastases at diagnosis and is associated with an excellent outcome due to its remarkable capacity to undergo spontaneous regression. As genomics have not been able to explain this intriguing clinical presentation, we here aimed at profiling the DNA methylome of stage 4S NB to better understand this phenomenon. To this purpose, differential methylation analyses between International Neuroblastoma Staging System (INSS) stage 4S, stage 4 and stage 1/2 were performed, using methyl-CpG-binding domain (MBD) sequencing data of 14 stage 4S, 14 stage 4, and 13 stage 1/2 primary NB tumors (all MYCN non-amplified in order not t…
Targeting the chromosomal passenger complex subunit INCENP induces polyploidization, apoptosis and senescence in neuroblastoma
2019
Abstract Chromosomal passenger complex (CPC) has been demonstrated to be a potential target of cancer therapy by inhibiting Aurora B or survivin in different types of cancer including neuroblastoma. However, chemical inhibition of either Aurora B or survivin does not target CPC specifically due to off-target effects or CPC-independent activities of these two components. In a previous chromatin-focused siRNA screen, we found that neuroblastoma cells were particularly vulnerable to loss of INCENP, a gene encoding a key scaffolding component of the CPC. In this study, INCENP was highly expressed by neuroblastoma cells, and its expression decreased following retinoic acid–induced neuroblastoma …
9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma.
2018
Advanced stage neuroblastoma is a very aggressive pediatric cancer with limited treatment options and a high mortality rate. Glycogen Synthase Kinase-3β (GSK-3β) is a potential therapeutic target in neuroblastoma. Using immunohistochemical staining, we observed positive GSK-3β expression in 67% of human neuroblastomas (34 out of 51 cases). Chemically distinct GSK-3 inhibitors (AR-A014418, TDZD8 and 9-ING-41), suppressed the growth of neuroblastoma cells whereas 9-ING-41, a clinically relevant small molecule GSK-3β inhibitor with broad spectrum pre-clinical antitumor activity, being the most potent. Inhibition of GSK-3 resulted in a decreased expression of the antiapoptotic molecule XIAP and…
Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-"decoy" strategy
2018
MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and …